Much human cancer originates in organs not vital to the life and well-being of the patient. Many of these malignant tumors retain to some extent the morphological and histological characteristics of the organs or tissues from which they are derived. We believe that such tumor cells are also likely to retain the antigenic characteristics of some of the normal cells of the tissues that underwent malignant change. If such an antigen is expressed on the surfaces of tumor cells, but not on cells vital to the life and well-being of the patient, this antigenic characteristic may provide a target for an attack on tumor by immunological mechanisms. We will look for such antigens in rats, by trying to prepare radioactive antibodies able, after i.v. injection, to localize with high specificity in tumors originating in mammary, large intestine, pancreas, and thyroid tissue. Antibodies will be sought in xenogeneic antisera. Because induced antibodies may cross-react with tissues of the immunized animal, we will also look for them in the crresponding target organs. Procedures used will include 125 I and 131 I labeling, in vitro purification of antibody by absorption with normal rat tissue excluding the organ of tumor origin, absorption and elution of antibody from insolubilized tumor tissue, and in vivo screening of labeled antibody in rats lacking the target organ. Radioactive tumor localizing antibody will be used as an immunological probe to identify the corresponding antigens during tumor cell fractionation studies. Such isolated antigens will then be used as immunogens to produce sera containing a larger fraction of tumor localizing antibody. The work of other investigators suggests multiple possibilities for the use of highly specific antibody and the corresponding antigen in the treatment of cancer. Thus positive results in demonstrating good in vivo localization in tumor of organ specific antibody will certainly suggest the possibility of the treatment of human tumors by methods based on these concepts.